# Metabolic Reprogramming in Insomnia as a Function of Objective Sleep Duration

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $672,473

## Abstract

Project Summary
Insomnia is among the most commonly experienced symptoms and is associated with significant distress and
impairment. The assessment of insomnia is reliant on patient self-report, which is often influenced by a number
of factors other than illness severity, complicating accurate diagnosis and treatment. Further, subtypes of
insomnia may exist based on the presence or absence of short sleep duration. Identification of a biological
‘signature’ of insomnia that could facilitate assessment and subtyping would dramatically improve symptom
management. Metabolic biomarkers have significant promise for meeting this need. Individuals with insomnia
demonstrate metabolic hyperarousal compared to good sleepers. Acute disruption of sleep in the laboratory
impacts the metabolome but the extent to which these findings extrapolate to chronic sleep disturbance or
insufficient sleep is unknown. Our own data indicate there is a clear metabolic signature that differentiates
patients with insomnia from good sleepers. The objective of this study is therefore to investigate the effects of
chronic insomnia and insufficient sleep on metabolic profiles. In order to test this hypothesis we will conduct in-
depth phenotyping of sleep and metabolism in 100 subjects who are in one of four groups (n=25 per group): 1)
patients with insomnia and objective short sleep (<6 hours) on actigraphy; 2) patients with insomnia without
objective short sleep (>6 hours); 3) habitual short sleepers (<6 hours) without evidence of insomnia; and 4)
good sleepers. Home overnight polysomnography and actigraphy will be used to rule out comorbid sleep
disordered breathing and confirm the presence of insomnia. All subjects will participate in a four-day inpatient
protocol in the Center for Human Phenomic Science. Food intake will be provided in hourly isocaloric snacks to
control for meal-induced shifts in metabolism. The first two days will be used to acclimate subjects to the
environment and meals. On the morning of day 3 they will have an indwelling catheter placed for blood
sampling every two hours for 48 hours with overnight polysomnography each night. During this time lighting
levels will be kept constantly dim (<250 lux) to minimize the effects of light exposure on circadian rhythms.
Metabolomics analysis of serum samples will be carried out using NMR and mass spectroscopy. Blood
samples will also be used for melatonin and cortisol assays as standard markers of circadian rhythmicity. The
global hypothesis that motivates this proposal is that chronic insomnia, insufficient sleep, and their combination
are associated with distinct profiles of systemic metabolic dysregulation.

## Key facts

- **NIH application ID:** 9862932
- **Project number:** 1R01NR018836-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Philip Richard Gehrman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $672,473
- **Award type:** 1
- **Project period:** 2020-07-27 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9862932

## Citation

> US National Institutes of Health, RePORTER application 9862932, Metabolic Reprogramming in Insomnia as a Function of Objective Sleep Duration (1R01NR018836-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9862932. Licensed CC0.

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